A quaternary phosphonium salt eugenol ester polymer antibacterial material and its synthesis method

Abstract

The present invention relates to a quaternary phosphonium salt eugenol ester polymer antibacterial material, which has the following structural formula: #imgabs0#; wherein: R is phenyl or butyl; X is an anion F ‑ 、Cl ‑ Br ‑ , I ‑ 、CN ‑ 、SCN ‑ 、BF4 ‑ PF6 ‑ OH ‑ or AlCl4 ‑ n1 is the degree of polymerization of the quaternary phosphonium salt eugenol ester antimicrobial monomer; Y is a regulating comonomer selected from N-vinyl pyrrolidone, styrene, 4-vinylbenzyl chloride, acrylic acid, acrylamide, or hydroxyethyl methacrylate; and n2 is the degree of polymerization of the comonomer. The present invention also discloses a method for synthesizing the material. The material has biodegradable properties and excellent antimicrobial activity and can be used in antimicrobial coatings, fruit and vegetable preservation, and the preparation of antimicrobial medical devices.

Description

Technical Field

[0001] The present invention relates to the technical field of functional polymer material synthesis, in particular to a quaternary phosphonium salt eugenol ester polymer antibacterial material and a synthesis method thereof. Background Art

[0002] Bacterial infections pose a serious threat to healthcare and agricultural production, and have become one of the most pressing public health issues. Antibiotic treatment is the most effective means of addressing bacterial infections. However, the overuse and abuse of antibiotics can lead to a sharp increase in bacterial resistance. According to the World Health Organization's annual management report, it is estimated that by 2050, 10 million people will die each year from drug-resistant bacterial infections, resulting in economic losses of up to US$2.7 billion. Even more worrying is that in the 21st century, the number of new antibiotics approved for clinical use each year is very small, making it difficult to address the growing threat of antibiotic resistance. Therefore, the development of new antibacterial materials to curb the spread of bacterial resistance has become an urgent issue that scientific researchers need to address.

[0003] In the post-antibiotic era, quaternary ammonium salts (QACs) have become a leading antimicrobial material due to their exceptional bactericidal properties and unique bactericidal mechanisms. However, QACs suffer from limitations such as poor drug resistance, slow biodegradation, and cytotoxicity, which limit their further application. Quaternary phosphonium salts (QPSs), a quaternary phosphonium salt with a structure closely resembling that of QACs, have phosphorus atoms with lower electronegativity and larger atomic radius than nitrogen atoms, and exhibit greater polarizability. Compared to their QAC counterparts, QPSs are weakly associated cations, enabling them to better adsorb to negatively charged bacterial membranes and exhibiting more reliable chemical stability, more efficient antimicrobial activity, enhanced resistance to bacterial resistance, and a wider range of applications. Therefore, QPSs offer greater advantages and potential than QACs in combating bacterial resistance. However, the utilization of quaternary phosphonium salts is generally divided into two categories: one involves grafting small organophosphorus molecules onto natural or synthetic polymers for modification. For example, Wang L, et al. (Effect of the structure of chitosanquaternary phosphonium salt andchitosanquaternary ammonium salt on the antibacterial and antibiofilm activity. International Journal of BiologicalMacromolecules, 2023, 242, 124877.) reported a method for preparing antibacterial and antibiofilm active materials by modifying chitosan with triphenylphosphine. Pan Q, et al. (Preparation and characterization ofchitosan derivatives modified withquaternary ammonium salt andquaternary phosphate salt and its effect ontropical fruit preservation. Food Chemistry, 2022, 387, 132878.) modified chitosan with (5-carboxypentyl)(triphenyl)phosphonium bromide and then composited it with polyvinyl alcohol to prepare a multifunctional food packaging composite film with excellent thermal stability and antibacterial properties.Tian W, et al. (Synthesis, characterization, and antifungal properties of starch derivatives modified with quaternaryphosphonium salts. Materials Science and Engineering: C, 2017, 76, 1048-1056.) reported the preparation of a modified starch material with excellent antifungal activity using triphenylphosphine-modified acetyl starch chloride. Patent (CN 116284497A) discloses a method for preparing chitosan grafted with a quaternary phosphonium salt; Patent (CN 118273112A) discloses a method for modifying polyacrylonitrile fibers with methyltriphenylphosphonium bromide to improve their mechanical properties and enhance their antibacterial properties; Patent (CN 118452227A) discloses a method for modifying cationic surfactants with quaternary phosphonium salts to enhance their dispersion, permeability, and bactericidal properties. Another approach involves functionalizing quaternary phosphonium salts with petroleum-based monomers to prepare polyquaternary phosphonium salt materials.For example, Wang L, et al. (Preparation and properties of quaternary phosphonium saltcontaining poly-acrylate emulsion. Progress in Organic Coatings, 2023, 175,107337.) synthesized methacryloyloxyethyltriphenylphosphonium bromide monomer and prepared polyacrylate quaternary phosphonium salt emulsion antibacterial material by seed emulsion polymerization; Cao P, et al. (Nano-assemblies of phosphonium-functionalizeddiblock copolymers with fabulous antibacterial properties andrelationships of structure-activity. Journal of Materials Chemistry B, 2022,10, 9202-9215.) and Sun X, et al. (Poly(phosphonium)-functionalizeddouble-armedβ-CD antimicrobial material via RAFT. Macromolecules, 2023, 56(23), 9498-9508.) reported a method for synthesizing a quaternary phosphonium salt antimicrobial monomer by quaternization of 4-vinylbenzyl chloride with triphenylphosphine, and then preparing a polyquaternary phosphonium salt antimicrobial material via RAFT polymerization. This method is protected by patent (CN116693721B). Patent (CN117025044A) discloses a water-based polyacrylate leather finishing agent with dual antimicrobial activity, using allyltriphenylphosphonium bromide as the primary antimicrobial monomer. Although numerous quaternary phosphonium salt antimicrobial materials have been reported, their further development has been hampered by issues such as high cytotoxicity and poor degradation. Therefore, balancing antimicrobial activity with cytotoxicity and degradability is a major challenge in the development of new QPS antimicrobial materials.

[0004] Bio-based compounds have attracted considerable attention in recent years, and utilizing them to improve the biocompatibility and sustainability of materials has become a novel strategy. For example, Chavarria, D. et al. (Phytochemicals and quaternaryphosphonium ionic liquids: Connecting the dots to develop a new class of antimicrobial agents. Journal of Advanced Research, 2023, 54, 251-269.) reported a tandem antimicrobial strategy utilizing natural products (such as gallic acid and caffeic acid) with quaternary phosphonium salts. However, this strategy did not achieve the organic integration of quaternary phosphonium salts with plant essential oils in polymers. Eugenol, a phenolic monoterpenoid extracted from various natural products such as clove oil and lignin, possesses advantages such as nontoxicity and easy degradation. Its unique allyl and phenolic functional groups make it amenable to chemical modification. Furthermore, its phenolic groups impart excellent antimicrobial activity and reactive oxygen species scavenging capabilities. For these reasons, eugenol is considered an emerging building block for the construction of a wide range of bio-based antimicrobial polymers. For example, Sha J, et al. (Surface hydrolysis-anchored eugenol self-polishing marine antifouling coating. Journal of Colloid and Interface Science, 2023, 637, 67-75.) (Eco-friendly self-polishing antifouling coating via eugenol esterhydrolysis. Progress in Organic Coatings, 2022, 172, 107077.) reported a method for preparing a self-polishing antimicrobial coating using methacrylate-functionalized eugenol. Kalita D, et al. (Poly (vinylethers) based on the biomass-derived compound, eugenol, and their one-component, ambient-cured surface coatings. Progress in Organic Coatings, 2022, 170, 106996.) reported a method for preparing a surface coating with high mechanical properties and stability using 2-chlorovinyl ether-modified eugenol.

[0005] Therefore, the present invention hopes to utilize renewable and biodegradable eugenol building blocks to functionalize QPS groups while ensuring antibacterial effects, further reducing the toxicity of QPS materials to cells, thereby giving them biocompatibility and environmental friendliness, and achieving a "win-win" goal. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to provide a quaternary phosphonium salt eugenol ester polymer antibacterial material with biodegradable properties and excellent antibacterial activity.

[0007] Another technical problem to be solved by the present invention is to provide a method for synthesizing the quaternary phosphonium salt eugenol ester polymer antibacterial material.

[0008] To solve the above problems, the present invention provides a quaternary phosphonium salt eugenol ester polymer antibacterial material, characterized in that the material has the following structural formula:

[0009] ;

[0010] Where: R is phenyl or butyl; X is an anion F - 、Cl - Br - , I - 、CN - 、SCN - 、BF4 - PF6 - OH - or AlCl4 - n1 is the degree of polymerization of the quaternary phosphonium salt eugenol ester antibacterial monomer; Y is one of the regulating comonomers N-vinyl pyrrolidone (NVP), styrene, 4-vinylbenzyl chloride, acrylic acid, acrylamide or hydroxyethyl methacrylate; n2 is the degree of polymerization of the comonomer.

[0011] The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material as described above is characterized in that: the method refers to using RAFT synthesis technology to controllably polymerize a quaternary phosphonium salt eugenol ester antibacterial monomer and a regulatory comonomer to obtain the material; the quaternary phosphonium salt eugenol ester antibacterial monomer refers to a triphenyl quaternary phosphonium salt eugenol ester antibacterial monomer or a tributyl quaternary phosphonium salt eugenol antibacterial monomer, which has the following structural formula:

[0012] ;

[0013] Where: R is phenyl or butyl; X is an anion F - 、Cl - Br - , I - 、CN - 、SCN - 、BF4- PF6 - OH - or AlCl4 - One of them.

[0014] The method for synthesizing the quaternary phosphonium salt eugenol ester polymer antibacterial material as described above comprises the following steps:

[0015] ⑴Synthesis of haloacetyl eugenol esters:

[0016] In a container A containing an excess of anhydrous solvent, eugenol and triethylamine are added in sequence. After stirring to dissolve, a haloacetyl halide is slowly added dropwise in an ice-water bath. After the addition is complete, stirring is continued at low temperature for 1 to 5 hours. The temperature is then raised to room temperature and the reaction is continued until it is fully reacted. After the reaction is completed, the temperature is cooled to 0°C to 10°C in an ice-water bath and deionized water is added to quench the reaction. The resulting reactant is extracted 1 to 3 times with a pure solvent. Finally, the resulting organic phase is dried over anhydrous magnesium sulfate, filtered, desolvated, and purified by column chromatography to obtain a haloacetyl eugenol ester.

[0017] ⑵Synthesis of quaternary phosphonium salt eugenol ester antibacterial monomer:

[0018] In a container B containing an excess of anhydrous solvent, haloacetyl eugenol ester and trialkylphosphine are added in sequence and stirred to dissolve. The resulting reaction solution is stirred and reacted at 65-85°C under an inert gas atmosphere for 12-24 hours. The reaction mixture is cooled to room temperature and the resulting reaction mixture is subjected to rotary evaporation and column chromatography purification to obtain a quaternary phosphonium salt eugenol ester antibacterial monomer.

[0019] ⑶Synthetic quaternary phosphonium salt eugenol ester polymer antibacterial material:

[0020] A quaternary phosphonium salt eugenol ester antibacterial monomer, a regulatory comonomer, a chain transfer agent (CTA), an initiator, and excess solvent were added to a Schlenk tube in sequence and stirred thoroughly to mix the reaction system evenly. The mass fractions of the monomer and chain transfer agent (CTA) in the system were fixed at 25% (w / w). The Schlenk tube was then subjected to three consecutive freeze-vacuum-nitrogen filling-thaw cycles to remove oxygen from the system. After the last cycle, the Schlenk tube was thawed to room temperature and then stirred at 60°C to 80°C for 12 hours to 24 hours. After completion of the reaction, the reaction was quenched with liquid nitrogen. Finally, the resulting reaction solution was transferred to an activated dialysis bag and dialyzed in deionized water. The deionized water was replaced every 3 hours. After dialysis, the components in the dialysis bag were freeze-dried to obtain the quaternary phosphonium salt eugenol ester polymer antibacterial material.

[0021] The solvents in steps (1) to (3) are methanol, ethanol, dichloromethane, chloroform, acetonitrile, 1,4-dioxane, N,N-dimethylformamide, tetrahydrofuran, acetone, dimethyl sulfoxide, or a mixture of two thereof.

[0022] In the step (1), the molar ratio of eugenol to triethylamine is 1.0:0.9 to 1.0:3.5.

[0023] In the step (1), the haloacetyl halide refers to chloroacetyl chloride or bromoacetyl bromide; the molar ratio of the eugenol to the haloacetyl halide is 1.0:1.0 to 1.0:4.0.

[0024] In step (2), the trialkylphosphine refers to triphenylphosphine or tributylphosphine; the molar ratio of the haloacetyleugenol ester to the trialkylphosphine is 1.0:1.1 to 1.0:2.5.

[0025] In step (2), the inert gas is nitrogen, argon or carbon dioxide.

[0026] In step (3), the molar ratio of the three raw materials, namely, the chain transfer agent (CTA), the quaternary phosphonium salt eugenol ester antibacterial monomer, and the regulating comonomer, is 1:20:20 to 1:80:80.

[0027] In step (3), the initiator is azobisisobutyronitrile (AIBN) or azobisisoheptanenitrile (ADVN), and its amount is 5% to 10% of the total mass of the reaction monomers.

[0028] The molecular weight cut-off of the dialysis bag in step (3) is 3000~14000 D.

[0029] The freeze-drying temperature in step (3) is -40 to -60°C.

[0030] Compared with the prior art, the present invention has the following advantages:

[0031] 1. The present invention uses eugenol, a plant essential oil with good biocompatibility, as a molecular building block, quaternary phosphonium salt as the main antibacterial component, different hydrophilic and hydrophobic monomers as regulatory comonomers, and haloacetyl halide as a connecting bridge. It successfully uses RAFT polymerization technology to prepare quaternary phosphonium salt eugenol ester polymer antibacterial nanomaterials with biodegradable properties and excellent antibacterial activity.

[0032] 2. The quaternary phosphonium salt eugenol ester polymer antibacterial material synthesized in the present invention has a high conversion rate, excellent antibacterial properties and good biocompatibility, and can be adjusted by changing the type of monomer and the degree of polymerization. It is a new antibacterial material with potential application prospects.

[0033] 3. The raw material eugenol used in the present invention has the advantages of good biocompatibility, wide source, and easy degradation, and can replace traditional petroleum-based monomers.

[0034] 4. The present invention has the characteristics of high reaction conversion rate, simple preparation process, easy availability of raw materials, good substrate tolerance, etc., and can provide a novel synthetic strategy for the synthesis of quaternary phosphonium salt eugenol ester copolymers.

[0035] 5. The quaternary phosphonium salt eugenol ester polymer prepared in the present invention can be used in antibacterial coatings, fruit and vegetable preservation, and can also be used in the preparation of antibacterial medical devices. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The specific embodiments of the present invention will be further described in detail below with reference to the accompanying drawings.

[0037] Figure 1 The H NMR spectrum of the phenyl quaternary phosphonium salt chloroeugenol ester antibacterial monomer prepared in Example 1 of the present invention is ( 1 HNMR).

[0038] Figure 2 The carbon NMR spectrum of the phenyl quaternary phosphonium salt chloroeugenol ester antibacterial monomer prepared in Example 1 of the present invention is ( 13 CNMR).

[0039] Figure 3 This is the infrared spectrum (FT-IR) of the phenyl quaternary phosphonium salt chloroeugenol ester antibacterial monomer prepared in Example 1 of the present invention.

[0040] Figure 4 The nuclear magnetic resonance hydrogen spectrum of the phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material prepared in Example 1 of the present invention is ( 1 H NMR).

[0041] Figure 5 The nuclear magnetic resonance phosphorus spectrum of the phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material prepared in Example 1 of the present invention is ( 31 P NMR).

[0042] Figure 6 This figure shows the effect of the antibacterial rate of the phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material prepared in Example 1 of the present invention on Escherichia coli and Staphylococcus aureus. DETAILED DESCRIPTION

[0043] A quaternary phosphonium salt eugenol ester polymer antibacterial material having the following structural formula:

[0044] ;

[0045] Where: R is phenyl or butyl; X is an anion F - 、Cl- Br - , I - 、CN - 、SCN - 、BF4 - PF6 - OH - or AlCl4 - n1 is the degree of polymerization of the quaternary phosphonium salt eugenol ester antibacterial monomer; Y is one of the regulating comonomers N-vinyl pyrrolidone (NVP), styrene, 4-vinylbenzyl chloride, acrylic acid, acrylamide or hydroxyethyl methacrylate; n2 is the degree of polymerization of the comonomer.

[0046] A method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material is disclosed. The method utilizes RAFT synthesis technology to controllably polymerize a quaternary phosphonium salt eugenol ester antibacterial monomer and a regulated comonomer to obtain the material. The quaternary phosphonium salt eugenol ester antibacterial monomer is a triphenyl quaternary phosphonium salt eugenol ester antibacterial monomer (R = phenyl) or a tributyl quaternary phosphonium salt eugenol antibacterial monomer (R = butyl), and has the following structural formula:

[0047] ;

[0048] Where: R is phenyl or butyl; X is an anion F - 、Cl - Br - , I - 、CN - 、SCN - 、BF4 - PF6 - OH - or AlCl4 - One of them.

[0049] The specific synthesis method comprises the following steps:

[0050] ⑴Synthesis of haloacetyl eugenol esters:

[0051] To container A containing excess anhydrous solvent, add eugenol and triethylamine sequentially, with the molar ratio of eugenol to triethylamine being 1.0:0.9 to 1.0:3.5. After stirring to dissolve, slowly add a haloacetyl halide dropwise in an ice-water bath (0°C to 5°C). The haloacetyl halide refers to chloroacetyl chloride or bromoacetyl bromide, with the molar ratio of eugenol to haloacetyl halide being 1.0:1.0 to 1.0:4.0. After the addition is complete, continue stirring at low temperature for 1 to 5 hours. Then, warm the mixture to room temperature and continue the reaction until complete. After the reaction is complete, cool the mixture to 0°C to 10°C in an ice-water bath and quench the reaction with deionized water. The resulting product is fractionally extracted with pure solvent 1 to 3 times. Finally, the resulting organic phase is dried over anhydrous magnesium sulfate, filtered, desolvated, and purified by column chromatography to obtain haloacetyl eugenol ester.

[0052] ⑵Synthesis of quaternary phosphonium salt eugenol ester antibacterial monomer:

[0053] To container B containing excess anhydrous solvent, add haloacetyl eugenol ester and trialkylphosphine, where triphenylphosphine or tributylphosphine is used, in sequence; the molar ratio of haloacetyl eugenol ester to trialkylphosphine is 1.0:1.1 to 1.0:2.5. After stirring and dissolving, the resulting reaction solution is stirred at 65-85°C under an inert gas atmosphere for 12-24 hours. The resulting reaction mixture is then cooled to room temperature, and the solvent is removed by rotary evaporation. The crude product is purified by column chromatography to obtain a quaternary phosphonium salt eugenol ester antibacterial monomer. This monomer can be exchanged for anionic species using ion exchange technology.

[0054] The inert gas is one of nitrogen, argon or carbon dioxide.

[0055] ⑶Synthetic quaternary phosphonium salt eugenol ester polymer antibacterial material:

[0056] A quaternary phosphonium salt eugenol ester antimicrobial monomer, a control comonomer, a chain transfer agent (CTA), an initiator, and excess solvent were added sequentially to a Schlenk tube. The molar ratio of the CTA, quaternary phosphonium salt eugenol ester antimicrobial monomer, and control comonomer ranged from 1:20:20 to 1:80:80. The initiator was either azobisisobutyronitrile (AIBN) or azobisisoheptanenitrile (ADVN), with the amount being 5% to 10% of the total monomer mass. The reaction system was thoroughly stirred to ensure uniform mixing, and the mass fractions of the monomer and CTA in the system were fixed at 25% (w / w). The Schlenk tube was then subjected to three consecutive freeze-vacuum-nitrogen-fill-thaw cycles to remove any oxygen from the system. After the final cycle, the Schlenk tube was thawed to room temperature and then stirred at 60°C to 80°C for 12 to 24 hours to ensure complete monomer conversion. After the reaction is completed, the reaction is quenched with liquid nitrogen. Finally, the resulting reaction solution is transferred to an activated dialysis bag with a molecular weight cutoff of 3000-14000 D and dialyzed in deionized water. The deionized water is replaced every 3 hours. After the dialysis is completed, the components in the dialysis bag are freeze-dried at -40 to -60 °C to obtain the quaternary phosphonium salt eugenol ester polymer antibacterial material.

[0057] The above solvents are all one or a mixture of two of methanol, ethanol, dichloromethane, chloroform, acetonitrile, 1,4-dioxane, N,N-dimethylformamide, tetrahydrofuran, acetone, and dimethyl sulfoxide.

[0058] Example 1

[0059] ⑴Synthesis of chloroacetyl eugenol ester:

[0060] To a three-necked flask containing 40 mL of anhydrous dichloromethane, add eugenol (20 mmol) and triethylamine (40 mmol) sequentially and stir to dissolve. Then, transfer the reaction flask to an ice-water bath (0°C–5°C) and slowly add chloroacetyl chloride (40 mmol) dropwise. Stir at low temperature for 2 hours. Then, warm the flask to room temperature and continue the reaction until complete. Cool the flask to 0°C–10°C in an ice-water bath and quench the reaction by adding 20 mL of deionized water. Extract the flask three times with pure solvent. Collect the organic phase, add anhydrous magnesium sulfate (1.5 g), dry it, and filter and remove the solvent. The crude product is purified by column chromatography to obtain chloroacetyl eugenol ester.

[0061] ⑵Synthesis of phenyl quaternary phosphonium salt chloroeugenol ester antibacterial monomer:

[0062] Weigh 16 mmol of chloroacetyl eugenol and 30 mmol of triphenylphosphine in 30 mL of acetonitrile and stir to dissolve. The reaction mixture was then stirred at 60°C for 12 h under nitrogen. After the reaction, the solution was cooled to room temperature, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography to obtain the antibacterial monomer of phenyl quaternary phosphonium salt chloroeugenol.

[0063] ⑶Synthetic phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material:

[0064] To a Schlenk tube, phenylphosphonium salt chloroeugenol ester antimicrobial monomer (7.95 mmol), N-vinyl pyrrolidone (7.95 mmol), chain transfer agent (CTA) (0.198 mmol), 0.25 g AIBN, and 14.6 g N,N-dimethylformamide were added sequentially, and the reaction system was mixed thoroughly using magnetic stirring. The mass fractions of monomer and CTA in the system were fixed at 25% (w / w). The Schlenk tube was subjected to three consecutive freeze-vacuum-nitrogen-thaw cycles to remove oxygen from the system. After the final cycle, the Schlenk tube was thawed to room temperature and then stirred at 60°C for 12 h to ensure complete monomer conversion. After completion, the reaction was quenched with liquid nitrogen. The reaction solution was transferred to an activated dialysis bag and placed in 500 mL of deionized water for dialysis. The deionized water was replaced every 3 hours. After the dialysis was completed, the components in the dialysis bag were freeze-dried at -40 to -60 ° C to obtain a phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material.

[0065] The phenyl quaternary phosphonium salt chloroeugenol ester antibacterial monomer and phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material synthesized in Example 1 of the present invention were characterized, analyzed, and tested for performance using the following methods.

[0066]

Characterization Analysis

[0067] Figure 1 This is the nuclear magnetic resonance hydrogen spectrum of the antibacterial monomer of phenyl quaternary phosphonium salt chloroeugenol ester ( 1 H NMR). 1H NMR (CDCl3, 400 MHz, δ ppm): The multiplets from 7.41 to 7.76 ppm are attributed to aromatic hydrogens (h) on triphenylphosphine; the multiplets from 6.30 to 6.83 ppm are attributed to hydrogens on the phenyl ring (e) on the eugenol backbone; the multiplets from 5.00 to 6.00 ppm are attributed to hydrogens on the olefin double bonds (a, b, c) on the eugenol backbone; the singlet at 3.85 ppm is attributed to hydrogens on a typical methoxy group (f); the singlet at 3.65 ppm is attributed to methylene hydrogens on phosphine (g); and the multiplets from 3.25 to 3.31 ppm are attributed to methylene hydrogens on the allyl group of eugenol (d). This demonstrates the successful synthesis of the antibacterial monomer of phenyl quaternary phosphonium salt chloroeugenol ester.

[0068] Figure 2 This is the NMR carbon spectrum of the antibacterial monomer of phenyl quaternary phosphonium salt chloroeugenol ester ( 13 C NMR). 13 In the C NMR spectrum, the peaks of each carbon atom (CDCl3, 150 MHz, δ ppm) are: 166.4, 150.8, 138.6, 134.7, 133.8, 133.3, 133.2, 132.5, 130.1, 130.0, 128.8, 124.3, 123.7, 122.2, 120.4,116.0, 115.4, 114.2, 112.4,111.1, 109.9, 55.8, 39.9, 31.3, 166.4 ppm, which are the characteristic peaks of carbonyl carbon atom (e). The peaks from 112.4 to 150.8 ppm are The peaks at 111.1 and 109.9 ppm are attributed to carbon atoms on the aromatic rings of triphenylphosphine and eugenol; the peaks at 55.8 ppm are attributed to the carbon atoms (d) on the olefin double bond of eugenol; the peak at 39.9 ppm is attributed to the methylene carbon atom (c) on the allyl group of eugenol; and the peak at 31.3 ppm is attributed to the methylene carbon atom (f). This indicates that the antibacterial monomer of phenyl quaternary phosphonium salt chloroeugenol ester was successfully synthesized.

[0069] Figure 3 This is the infrared spectrum of the antibacterial monomer of phenyl quaternary phosphonium salt chloroeugenol ester. Each absorption peak (cm -1 ) and the corresponding functional groups are: 3059 (-CH3), 2960 (-CH2-), 1720 (-C=O), 1675 (-C=C), 1600 (-Ph), 1450 (-Ph), 1110 (-COC), 1035 (-COC), and 690 (-CP). This further demonstrates the successful synthesis of the antibacterial monomer phenyl quaternary phosphonium salt chloroeugenol ester.

[0070] Figure 4 The nuclear magnetic hydrogen spectrum of the antibacterial material of phenyl quaternary phosphonium salt chloroeugenol ester polymer ( 1 H NMR) diagram. 1 In the H NMR spectrum, multiplets from 6.70 to 7.19 ppm are attributed to the aromatic hydrogens of triphenylphosphine (k); multiplets from 5.97 to 6.28 ppm are attributed to the aromatic hydrogens of the eugenol skeleton (h); a singlet peak at 3.30 ppm is attributed to the methoxy hydrogens of eugenol (i); a singlet peak at 3.12 ppm is attributed to the methylene hydrogens of phosphine (j); a peak at 2.68 ppm is attributed to the methylene hydrogens of the allyl group (g); and peaks from 0.31 to 1.83 ppm are attributed to the hydrogens of the small molecule chain transfer agent. Furthermore, no signal peaks were detected for olefin double bonds, indicating that the olefin double bonds participated in the polymerization reaction. This demonstrates the successful preparation of antibacterial polymers based on phenyl quaternary phosphonium salt chloroeugenol esters.

[0071] Figure 5 The nuclear magnetic phosphorus spectrum of the antibacterial material of phenyl quaternary phosphonium salt chloroeugenol ester polymer ( 31 P NMR) diagram. 31 P NMR analysis revealed a typical broad peak for the phenyl quaternary phosphonium salt chloroeugenol ester polymer antimicrobial material, with a chemical shift of 21.24 ppm, consistent with the peak shift of the phosphorus atom. This confirmed the correct structure and purity of the prepared phenyl quaternary phosphonium salt chloroeugenol ester polymer antimicrobial material, demonstrating successful preparation.

[0072]

Antibacterial properties

[0073] Select Escherichia coli ( E. coli ) and Staphylococcus aureus ( S. aureus ) as a bacterial model, a certain amount of solid culture medium was prepared, and the plate count method was used to test the antibacterial properties of phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material. Figure 6 The effect of the concentration of phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material on the inhibition rate of Escherichia coli and Staphylococcus aureus. Due to the presence of quaternary phosphonium salt chloroeugenol ester antibacterial material, phenyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material showed excellent antibacterial activity, and the inhibition rate of Escherichia coli and Staphylococcus aureus was 1.3777% after 24 hours. E. coli and S. aureus The antibacterial rate can reach 100%.

[0074] Example 2

[0075] ⑴Synthesis of bromoacetyl eugenol ester:

[0076] To a three-necked flask containing 50 mL of anhydrous dichloromethane, add eugenol (30 mmol) and triethylamine (48 mmol) sequentially and stir to dissolve. Then, transfer the reaction flask to an ice-water bath (0°C–5°C) and slowly add bromoacetyl bromide (48 mmol) dropwise. After the addition is complete, continue stirring at low temperature for 1 hour. Then, warm the flask to room temperature and continue the reaction until complete. Cool the flask to 0°C–10°C in an ice-water bath and quench the reaction by adding 30 mL of deionized water. Extract the mixture twice with pure solvent, collect the organic phase, dehydrate and dry it over anhydrous magnesium sulfate (2 g), filter, and remove the solvent. The crude product is purified by column chromatography to obtain bromoacetyl eugenol ester.

[0077] The crude product was purified by column chromatography.

[0078] ⑵Synthesis of phenyl quaternary phosphonium salt bromoeugenol ester antibacterial monomer:

[0079] Weigh 20 mmol of bromoacetyl eugenol ester and 38 mmol of triphenylphosphine in 30 mL of acetonitrile and stir to dissolve. The reaction mixture was then stirred at 70°C under argon for 18 h. After the reaction, the solution was cooled to room temperature, and the solvent was removed by rotary evaporation. The crude product was purified by column chromatography to obtain the antibacterial monomer of phenyl quaternary phosphonium salt bromoeugenol ester.

[0080] ⑶Synthetic phenyl quaternary phosphonium salt bromoeugenol ester polymer antibacterial material:

[0081] To a Schlenk tube, phenylphosphonium salt bromoeugenol ester antibacterial monomer (7.95 mmol), N-vinyl pyrrolidone (7.95 mmol), chain transfer agent (CTA) (0.198 mmol), 5.22 mg of AIBN, and 15 g of N,N-dimethylformamide were added sequentially, and the reaction system was mixed thoroughly using magnetic stirring. The mass fraction of monomer and CTA in the system was fixed at 25% (w / w). The Schlenk tube was subjected to three consecutive freeze-vacuum-nitrogen-thaw cycles to remove oxygen from the system. After the final cycle, the Schlenk tube was thawed to room temperature and then stirred at 70°C for 18 hours to ensure complete monomer conversion. After completion, the reaction was quenched with liquid nitrogen. The reaction solution was transferred to an activated dialysis bag and placed in 500 mL of deionized water for dialysis. Clean deionized water was replaced every 3 hours. After the dialysis was completed, the components in the dialysis bag were freeze-dried at -40 ~ -60 ° C to obtain phenyl quaternary phosphonium salt bromoeugenol ester polymer antibacterial material.

[0082] Example 3

[0083] ⑴Synthesis of chloroacetyl eugenol ester:

[0084] To a three-necked flask containing 50 mL of anhydrous dichloromethane, add eugenol (30 mmol) and triethylamine (45 mmol) sequentially and stir to dissolve. Then, transfer the reaction flask to an ice-water bath (0°C–5°C) and slowly add chloroacetyl chloride (45 mmol) dropwise. Stir at low temperature for 2 hours. Then, warm the flask to room temperature and continue the reaction until complete. Cool the flask to 0°C–10°C in an ice-water bath and quench the reaction by adding 30 mL of deionized water. Extract the flask three times with pure solvent. Collect the organic phase, add anhydrous magnesium sulfate (2.5 g), dry it, and filter and remove the solvent. The crude product is purified by column chromatography to obtain chloroacetyl eugenol ester.

[0085] ⑵Synthesis of butyl quaternary phosphonium salt chloroeugenol ester antibacterial monomer:

[0086] Weigh 30 mmol of chloroacetyl eugenol and 38 mmol of tributyl phosphine into 30 mL of solvent and stir to dissolve. The reaction mixture was then stirred at 80°C under nitrogen for 24 h. After the reaction, the solution was cooled to room temperature, and the solvent was removed from the reaction mixture using a rotary evaporator. The crude product was purified by column chromatography to obtain the antibacterial monomer of butyl quaternary phosphonium salt chloroeugenol as a red oil.

[0087] ⑶Synthetic butyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material:

[0088] A Schlenk tube was sequentially added with butyl quaternary phosphonium salt chloroeugenol ester antimicrobial monomer (11.93 mmol), N-vinyl pyrrolidone (11.93 mmol), chain transfer agent (CTA) (0.297 mmol), 0.732 g AIBN, and 22 g N,N-dimethylformamide. The reaction system was mixed thoroughly using magnetic stirring. The mass fractions of monomer and CTA in the system were fixed at 25% (w / w). The Schlenk tube was subjected to three consecutive freeze-vacuum-nitrogen-thaw cycles to remove oxygen from the system. After the final cycle, the Schlenk tube was thawed to room temperature and then stirred at 80°C for 24 h to ensure complete monomer conversion. After completion, the reaction was quenched with liquid nitrogen. The reaction solution was transferred to an activated dialysis bag and placed in 500 mL of deionized water for dialysis. Clean deionized water was replaced every 3 hours. After the dialysis was completed, the components in the dialysis bag were freeze-dried at -40 ~ -60 ° C to obtain butyl quaternary phosphonium salt chloroeugenol ester polymer antibacterial material.

Claims

1. A quaternary phosphonium salt eugenol ester polymer antibacterial material, characterized in that: The material has the following structural formula: ； Where: R is phenyl or butyl; X is an anion F - 、Cl - Br - , I - 、CN - 、SCN - 、BF4 - PF6 - OH - or AlCl4 - n1 is the degree of polymerization of the quaternary phosphonium salt eugenol ester antibacterial monomer; Y is one of the regulating comonomers N-vinyl pyrrolidone, styrene, 4-vinylbenzyl chloride, acrylic acid, acrylamide or hydroxyethyl methacrylate; n2 is the degree of polymerization of the comonomer.

2. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 1, wherein: The method adopts RAFT synthesis technology to controllably polymerize a quaternary phosphonium salt eugenol ester antibacterial monomer and a regulating comonomer to obtain the obtained product; the quaternary phosphonium salt eugenol ester antibacterial monomer refers to a triphenyl quaternary phosphonium salt eugenol ester antibacterial monomer or a tributyl quaternary phosphonium salt eugenol antibacterial monomer, which has the following structural formula: ； Where: R is phenyl or butyl; X is an anion F - 、Cl - Br - , I - 、CN - 、SCN - 、BF4 - PF6 - OH - or AlCl4 - One of them.

3. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 2, comprising the following steps: ⑴Synthesis of haloacetyl eugenol esters: In a container A containing an excess of anhydrous solvent, eugenol and triethylamine are added in sequence. After stirring to dissolve, a haloacetyl halide is slowly added dropwise in an ice-water bath. After the addition is complete, stirring is continued at low temperature for 1 to 5 hours. The temperature is then raised to room temperature and the reaction is continued until it is fully reacted. After the reaction is completed, the temperature is cooled to 0°C to 10°C in an ice-water bath and deionized water is added to quench the reaction. The resulting reactant is extracted 1 to 3 times with a pure solvent. Finally, the resulting organic phase is dried over anhydrous magnesium sulfate, filtered, desolvated, and purified by column chromatography to obtain a haloacetyl eugenol ester. ⑵Synthesis of quaternary phosphonium salt eugenol ester antibacterial monomer: In a container B containing an excess of anhydrous solvent, haloacetyl eugenol ester and trialkylphosphine are added in sequence and stirred to dissolve. The resulting reaction solution is stirred and reacted at 65-85°C under an inert gas atmosphere for 12-24 hours. The reaction mixture is cooled to room temperature and the resulting reaction mixture is subjected to rotary evaporation and column chromatography purification to obtain a quaternary phosphonium salt eugenol ester antibacterial monomer. ⑶Synthetic quaternary phosphonium salt eugenol ester polymer antibacterial material: A quaternary phosphonium salt eugenol ester antibacterial monomer, a regulatory comonomer, a chain transfer agent, an initiator, and excess solvent were added to a Schlenk tube in sequence and stirred thoroughly to mix the reaction system evenly. The mass fractions of the monomer and chain transfer agent in the system were fixed at 25%. The Schlenk tube was then subjected to three consecutive freeze-vacuum-nitrogen filling-thaw cycles to remove oxygen from the system. After the last cycle, the Schlenk tube was thawed to room temperature and stirred at 60°C to 80°C for 12 hours to 24 hours. After completion of the reaction, the reaction was quenched with liquid nitrogen. Finally, the resulting reaction solution was transferred to an activated dialysis bag and dialyzed in deionized water, with the deionized water replaced every 3 hours. After dialysis, the components in the dialysis bag were freeze-dried to obtain the quaternary phosphonium salt eugenol ester polymer antibacterial material.

4. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: The solvents in steps (1) to (3) are methanol, ethanol, dichloromethane, chloroform, acetonitrile, 1,4-dioxane, N,N-dimethylformamide, tetrahydrofuran, acetone, dimethyl sulfoxide, or a mixture of two thereof.

5. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: In the step (1), the molar ratio of eugenol to triethylamine is 1.0:0.9 to 1.0:3.

5.

6. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: In the step (1), the haloacetyl halide refers to chloroacetyl chloride or bromoacetyl bromide; the molar ratio of the eugenol to the haloacetyl halide is 1.0:1.0 to 1.0:4.

0.

7. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: In step (2), the trialkylphosphine refers to triphenylphosphine or tributylphosphine; the molar ratio of the haloacetyleugenol ester to the trialkylphosphine is 1.0:1.1 to 1.0:2.

5.

8. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: In step (2), the inert gas is nitrogen, argon or carbon dioxide.

9. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: In step (3), the molar ratio of the three raw materials, namely, the chain transfer agent, the quaternary phosphonium salt eugenol ester antibacterial monomer, and the regulating comonomer, is 1:20:20 to 1:80:

80.

10. The method for synthesizing a quaternary phosphonium salt eugenol ester polymer antibacterial material according to claim 3, wherein: In step (3), the initiator is azobisisobutyronitrile or azobisisoheptanenitrile, and its amount is 5% to 10% of the total mass of the reaction monomers.

Images